Duloxetine is a selective serotonin and norepinephrine reuptake inhibitors (SNRIs). It is a safe and effective antidepressant drug. Its chemical designation is (+)-(S)—N-methyl-γ-(1-naphthyloxy)2-thiophenepropylamine. It is usually used in the form of its hydrochloride. As duloxetine is unstable and easily degraded in acidic condition, it is suitable to make duloxetine or its salts into enteric formulation to resist the corrosion of gastric juice.
U.S. Pat. No. 5,508,276 relates to a kind of duloxetine enteric pellet, which comprising a) a core consisting of duloxetine and a pharmaceutically acceptable excipient; b) an optional separating layer; c) an enteric layer comprising hydroxypropyl methylcellulose acetate succinate (HPMCAS) and a pharmaceutically acceptable excipient; d) an optional finishing layer. In the separating layer, sugar alleviates the migration and interaction between enteric coating material and duloxetine to improve the acid resistance and stability.
Z1200410067160.4 relates to a kind of duloxetine enteric coating tablet and manufacturing process thereof. Duloxetine hydrochloride, water-soluble solid disperse carrier and thinner are dissolved in ethanol aqueous; it is to be sieved and pelletized, dried, granulated, added lubricant and then preformed using the methods commonly known in this field; and the tablet core is coated with separating layer and the separating layer is coated with enteric layer. This method uses solid dispersion technology, increases the solubility of the main drug and improves the final release amount so as to improve the bioavailability of duloxetine.
Duloxetine easily tends to take place reactions of degradation etc. In which water plays an accelerated or catalytic role. As for the published duloxetine hydrochloride enteric formulation, during the manufacture of the medicine core of duloxetine hydrochloride, the solution or suspension of duloxetine hydrochloride is made first, or the wetting agent or adhesion agent is added first, and in both conditions, duloxetine hydrochloride has contacted with water and some organic solvents such as ethanol, which influences the stability of duloxetine hydrochloride; moreover, when removing the water or the organic solvents, it wastes time and labor force and increases cost, and the unstable factor will also be increased. If the organic solvents are used, it will be an environmental pollution.